- Chemical Synthesis and Analysis
- Biochemical and Structural Characterization
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Carbohydrate Chemistry and Synthesis
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- Microbial Natural Products and Biosynthesis
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Catalytic C–H Functionalization Methods
- Synthesis and Catalytic Reactions
- Advanced biosensing and bioanalysis techniques
- Antimicrobial Peptides and Activities
- DNA and Nucleic Acid Chemistry
- Biochemical and Molecular Research
- Catalytic Processes in Materials Science
- Enzyme Production and Characterization
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- HIV/AIDS drug development and treatment
- TiO2 Photocatalysis and Solar Cells
- Cancer-related gene regulation
Chinese University of Hong Kong
2024
Nanyang Technological University
2015-2024
Institute of Soil Science
2024
Chinese Academy of Sciences
2024
Nanjing Tech University
2019-2022
Beijing Graphene Institute
2020
Singapore-MIT Alliance for Research and Technology
2019
Vanderbilt University
1994-2006
Amgen (United States)
1998-2006
Vanderbilt University Medical Center
1996
Lysine acetylation and its regulatory enzymes are known to have pivotal roles in mammalian cellular physiology. However, the extent function of this modification prokaryotic cells remain largely unexplored, thereby presenting a hurdle further functional study systems. Here we report first global screening lysine acetylation, identifying 138 sites 91 proteins from Escherichia coli. None has been previously associated with modification. Among identified transcriptional regulators, as well...
Chemical modification of transcripts with 5' caps occurs in all organisms. Here, we report a systems-level mass spectrometry-based technique, CapQuant, for quantitative analysis an organism's cap epitranscriptome. The method was piloted 21 canonical caps-m7GpppN, m7GpppNm, GpppN, GpppNm, and m2,2,7GpppG-and 5 'metabolite' caps-NAD, FAD, UDP-Glc, UDP-GlcNAc, dpCoA. Applying CapQuant to RNA from purified dengue virus, Escherichia coli, yeast, mouse tissues, human cells, discovered new...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical Ligation Approach To Form a Peptide Bond between Unprotected Segments. Concept and Model StudyChuan-Fa Liu James P. TamCite this: J. Am. Chem. Soc. 1994, 116, 10, 4149–4153Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 1994https://pubs.acs.org/doi/10.1021/ja00089a001https://doi.org/10.1021/ja00089a001research-articleACS PublicationsRequest reuse permissionsArticle...
A thiol group introduced on the γ-carbon of lysine mediates robust native chemical ligation at both α- and ε-amines in two consecutive steps. Desulfurization then affords final product, which residue site has an isopeptide bond its side chain. The method is useful for synthesis proteins containing special post-translational modifications lysine.
We describe an approach to the synthesis of peptides from segments bearing no protecting groups through orthogonal coupling method capture acyl segment as a thioester that then undergoes intramolecular transfer amine component with formation peptide bond. Two methods give covalent ester intermediate were achieved by either thiol-thioester exchange mediated trialkylphosphine and alkylthiol or thioesterification C alpha-thiocarboxylic acid reacting beta-bromo amino acid. With this approach,...
Understanding the molecular mechanisms behind regulation of chromatin folding through covalent modifications histone N-terminal tails is hampered by a lack accessible containing precisely modified histones. We study internal and intermolecular self-association system consisting saturated 12-mer nucleosome arrays various combinations completely acetylated lysines at positions 5, 8, 12 16 H4, induced cations Na + , K Mg 2+ Ca cobalt-hexammine 3+ spermidine spermine 4+ . Histones were prepared...
We describe the concept and verification of a chemical ligation approach to synthesis proteins using peptide segments with no protecting groups activation C-terminal alpha-carboxyl group. This consists three steps: (i) aldehyde introduction, in which masked glycolaldehyde ester is linked carboxyl terminus an unprotected by reverse proteolysis; (ii) ring formation, unmasked reacts N-terminal alpha-amino group second containing either cysteine or threonine residue form thiazolidine oxazolidine...
Radicals at work: Radical-mediated thiol-ene addition of the thiol group Cys to N-vinylacetamide gives acetyl-thialysine (KSAc), a near-perfect mimic acetyl-lysine (see picture). The reaction is highly efficient with near quantitative conversion obtained in short times. generated KSAc functionally identical or similar its native counterpart.
Asparaginyl endopeptidases (AEPs) are cysteine proteases which break Asx (Asn/Asp)–Xaa bonds in acidic conditions. Despite sharing a conserved overall structure with AEPs, certain plant enzymes such as butelase 1 act peptide asparaginyl ligase (PAL) and catalyze Asx–Xaa bond formation near-neutral PALs also serve macrocyclases the biosynthesis of cyclic peptides. Here, we address question how PAL can function rather than protease. Based on sequence homology 1, identified AEPs from...
Abstract An efficient ligase with exquisite site‐specificity is highly desirable for protein modification. Recently, we discovered the fastest known called butelase 1 from Clitoria ternatea intramolecular cyclization. For intermolecular ligation, requires an excess amount of a substrate to suppress reverse reaction, feature similar other ligases. Herein, describe use thiodepsipeptide substrates thiol as leaving group and unacceptable nucleophile render butelase‐mediated ligation reactions...
Abstract Histone lysine methylations have primarily been linked to selective recruitment of reader or effector proteins that subsequently modify chromatin regions and mediate genome functions. Here, we describe a divergent role for histone H4 20 mono-methylation (H4K20me1) demonstrate it directly facilitates openness accessibility by disrupting folding. Thus, accumulation H4K20me1 demarcates highly accessible at genes, this is maintained throughout the cell cycle. In vitro,...
Infections caused by drug-resistant bacteria seriously endanger human health and global public health. Therefore, it is urgent to discover develop novel antimicrobial agents combat multidrug-resistant bacteria. In this study, we designed synthesized a series of new membrane-active bakuchiol derivatives biomimicking the structure function cationic antibacterial peptides. The most promising compound 28 displayed potent activity against both Gram-positive (minimum inhibitory concentration, MIC...
With two β-mercaptoethyl groups on the N, a tertiary amide of structure 1 is always poised for intramolecular thioesterification however it flips about C−N bond. It shown that peptide with such C-terminal N,N-bis(2-mercaptoethyl)-amide (BMEA) can be used directly native chemical ligation (NCL). These BMEA peptides are easily prepared standard Fmoc-solid phase synthesis protocols, thus giving very convenient access to thioester components NCL.
Recombinant proteins with a C-terminal thioester are readily prepared through the catalysis of butelase 1 – powerful peptide ligase.
Butelase-mediated ligation (BML) can be used to modify live bacterial cell surfaces with diverse cargo molecules. Surface-displayed butelase recognition motif NHV was first introduced at the C-terminal end of anchoring protein OmpA on E. coli cells. This then served as a handle BML for functionalization fluorescein and biotin tags, tumor-associated monoglycosylated peptide, mCherry protein. The cell-surface reaction achieved low concentrations labeling substrates. Furthermore,...
Enzymatic peptide ligation holds great promise in the study of protein functions and development therapeutics. Owing to their high catalytic efficiency a minimal tripeptide recognition motif, peptidyl asparaginyl ligases (PALs) are particularly useful tools for bioconjugation. However, as an inherent limitation transpeptidases, PAL-mediated is reversible, requiring large excess one partners shift reaction equilibrium forward direction. Herein, we report method make intermolecular...
Abstract Disulfides in peptides and proteins are essential for maintaining a properly folded structure. Their oxidative folding is invariably performed an aqueous‐buffered solution. However, this process often slow can lead to misfolded products. Here, we report novel concept strategy that bio‐inspired mimic protein disulfide isomerase (PDI) by accelerating exchange rates many thousand‐fold. The proposed termed organic under solvents yield correctly cysteine‐rich microproteins...
The dual native chemical ligation at lysine strategy was revised by replacing the acid-labile Cbz protecting group with photolabile NVOC 4-mercaptolysine side chain. optimized subsequently applied to synthesis of K48-linked diubiquitin.